LiHMDS-Mediated Deprotonative Coupling of Toluenes with Ketones

Masanori Shigeno; Akihisa Kajima; Eito Toyama; Toshinobu Korenaga; Hiroyuki Yamakoshi; Kanako Nozawa-Kumada; Yoshinori Kondo

doi:10.1002/chem.202203549

LiHMDS-Mediated Deprotonative Coupling of Toluenes with Ketones

Chemistry. 2023 Mar 13;29(15):e202203549. doi: 10.1002/chem.202203549. Epub 2023 Feb 13.

Authors

Masanori Shigeno^{1

2}, Akihisa Kajima¹, Eito Toyama¹, Toshinobu Korenaga^{3

4}, Hiroyuki Yamakoshi⁵, Kanako Nozawa-Kumada¹, Yoshinori Kondo¹

Affiliations

¹ Department of Biophysical Chemistry Graduate School of Pharmaceutical Science, Tohoku University, 6-3 Aoba, Sendai, 980-8578, Japan.
² JST, PRESTO, Kawaguchi, Saitama, 332-0012, Japan.
³ Department of Chemistry and Biological Sciences Faculty of Science and Engineering, Iwate University Ueda, Morioka, 020-8551, Japan.
⁴ Soft-Path Science and Engineering Research Center (SPERC), Iwate University, Ueda, Morioka, 020-8551, Japan.
⁵ Central Analytical Center, Graduate School of Pharmaceutical Science, Tohoku University, 6-3 Aoba, Sendai, 980-8578, Japan.

PMID: 36479733
DOI: 10.1002/chem.202203549

Abstract

We demonstrate that lithium hexamethyldisilazide (LiHMDS) acts as an effective base for deprotonative coupling reactions of toluenes with ketones to afford stilbenes. Various functionalities (halogen, OCF₃ , amide, Me, aryl, alkenyl, alkynyl, SMe, and SPh) are allowed on the toluenes. Notably, this system proved successful with low-reactive toluenes bearing a large pKa value compared to that of the conjugate acid of LiHMDS (hexamethyldisilazane, 25.8, THF), as demonstrated by 4-phenyltoluene (38.57, THF) and toluene itself (∼43, DMSO).

Keywords: amide-base; deprotonative coupling; ketones; olefination; toluenes.